High plasma CD40 ligand level is associated with more advanced stages and worse prognosis in colorectal cancer

Zoltan Herold; Magdolna Herold; Gyorgy Herczeg; Agnes Fodor; Attila Marcell Szasz; Magdolna Dank; Aniko Somogyi

doi:10.12998/wjcc.v10.i13.4084

High plasma CD40 ligand level is associated with more advanced stages and worse prognosis in colorectal cancer

World J Clin Cases. 2022 May 6;10(13):4084-4096. doi: 10.12998/wjcc.v10.i13.4084.

Authors

Zoltan Herold¹, Magdolna Herold², Gyorgy Herczeg³, Agnes Fodor³, Attila Marcell Szasz¹, Magdolna Dank¹, Aniko Somogyi²

Affiliations

¹ Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, Budapest H-1083, Hungary.
² Department of Internal Medicine and Hematology, Semmelweis University, Budapest H-1088, Hungary.
³ Department of General Surgery, Szent Imre University Teaching Hospital, Budapest H-1115, Hungary.

Abstract

Background: Colorectal cancer (CRC) is often associated with elevated platelet count (> 400 × 10⁹/L), known as thrombocytosis. The role of CD40 ligand (CD40L), a member of the tumor necrosis factor family, is controversial in CRC. Circulating CD40L is higher in CRC, but its relationship with disease staging and local and distant metastasis is not clear. Although most of the circulating CD40L is produced by platelets, no previous study investigated its relationship with CRC-related thrombocytosis.

Aim: To investigate the role of CD40L to predict the outcome of CRC and its relation to thrombocytosis.

Methods: A total of 106 CRC patients and 50 age and sex-matched control subjects were enrolled for the study. Anamnestic data including comorbidities and histopathological data were collected. Laboratory measurements were performed at the time of CRC diagnosis and 1.5 mo and at least 6 mo after the surgical removal of the tumor. Plasma CD40L and thrombopoietin were measured via enzyme-linked immunosorbent assay, while plasma interleukin-6 was measured via electrochemiluminescence immunoassay. Patient follow-ups were terminated on January 31, 2021.

Results: Plasma CD40L of CRC patients was tendentiously higher, while platelet count (P = 0.0479), interleukin-6 (P = 0.0002), and thrombopoietin (P = 0.0024) levels were significantly higher as opposed to the control subjects. Twelve of the 106 CRC patients (11.3%) had thrombocytosis. Significantly higher CD40L was found in the presence of distant metastases (P = 0.0055) and/or thrombocytosis (P = 0.0294). A connection was found between CD40L and platelet count (P = 0.0045), interleukin-6 (P = 0.0130), and thrombocytosis (P = 0.0155). CD40L was constant with the course of CRC, and all baseline differences persisted throughout the whole study. Both pre- and postoperative elevated platelet count, CD40L, and interleukin-6 level were associated with poor overall and disease-specific survival of patients. The negative effect of CD40L and interleukin-6 on patient survival remained even after the stratification by thrombocytosis.

Conclusion: CD40L levels of CRC patients do not change with the course of the disease. The CD40L level is strongly correlated with platelet count, interleukin-6, thrombocytosis, and the presence of distant metastases.

Keywords: CD40 ligand; Colorectal neoplasms; Interleukin-6; Thrombocytosis; Thrombopoietin.